Since the identification of the fetal alcohol syndrome two decades ago, the adverse reproductive effects of heavy maternal drinking and maternal alcohol abuse in pregnancy have been well documented. Many research areas related to alcohol's effects as a reproductive toxin remain unexplored or underexplored, however. We are proposing to conduct analyses of the effects of each parent's drinking before and during pregnancy, and of the interactive effects of parental drinking and exposures to occupational and environmental toxicants, on pregnancy and birth outcomes (stillbirth, birth size, gestational age, intrauterine growth). We will conduct the proposed analyses using data collected as part of the ongoing Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC), a project of the University of Bristol (England) Institute of Child Health conducted under the aegis of the World Health Organization. ALSPAC staff have attempted to recruit all pregnant residents of Avon County (excluding the Bath health district) whose pregnancies end in a live birth or fetal death between 1 April 1991 and 31 December 1992, inclusive. Participants' male partners are also enrolled whenever possible. The final ALSPAC cohort will contain at least 15,000 women (and their infants)and 9,000 male partners. Information on each parent's exposures before and during the index pregnancy (including information on alcohol use and exposures to occupational and environmental toxicants) is obtained through a series of self-administered questionnaires completed by both women and men during the index pregnancy. The relationships between each parent's drinking habits before and during pregnancy and each of the pregnancy and birth outcomes of interest will be examined by means of crude bivariate, stratified, and multivariate regression analyses. Particular attention will be paid to the timing of alcohol exposure relative to pregnancy and to the specific pattern of alcohol exposure (e.g., chronic lower dose exposure versus sporadic peak exposures). The presence of alcohol-toxicant interactions will also be assessed for both women and men by comparing the risks of adverse pregnancy and birth outcomes among those exposed to alcohol alone, the occupational or environmental agent alone, and both together relative to those exposed to neither alcohol nor the toxicant. These analyses will focus on ethanol-solvent and ethanol-metal interactions. Solvents and metals have received the most attention to date in the experi- mental and toxicologic literature on interactions and are also among the most prevalent occupational hazards. The Avon study is the largest prospective, population-based follow-up study of pregnancy and childhood to be undertaken in the past several decades. It is unique in that information on paternal and maternal exposures prior to and during pregnancy has been obtained directly from both fathers and mothers, rather than by proxy or by record. Its data base represents an important resource for epidemiologic studies of reproductive outcomes, particularly those related to the effects of parental drinking.